Phospholipase A.sub.2 (PLA.sub.2) is a calcium-dependent enzyme which cleaves the R-2 acyl group of phospholipids. In mammalian tissues, this cleavage primarily yields free arachidonic acid which can then be converted by the cyclooxygenase system to prostaglandins and thromboxanes. Alternatively, arachidonic acid can be converted into leukotrienes via the lipoxygenase pathway. See generally G. Weissman, Cellular Immunology, 82, 117 (1983). See also E. Israel and J. M. Drazen, "Leukotrienes and Asthma: A Basic Review" in Current Concepts in Allergy and Clinical Immunology, Vol XIV, No 3. pp. 11-16 (1983).
Many anti-inflammatory agents, such as aspirin, indomethacin, and ibuprofen, block the formation of prostaglandins by inhibiting the cyclooxygenase pathway. Similarly, inhibition of the lipoxygenase pathway, and therefore the formation of leukotrienes, has also been shown to produce an anti-inflammatory effect. An inhibitor of PLA.sub.2, which would prevent the release of arachidonic acid, would effectively block both pathways and should be an effective anti-inflammatory agent by inhibiting the production of mediators from both pathways.
It is the purpose of this invention to provide certain furanone derivatives which are useful as anti-inflammatory and anti-allergy agents by virtue of their ability to inhibit the enzyme PLA.sub.2.